Cell adhesion and morphogenesis are crucial events in craniofacial development, and errors can result in congenital anomalies. Related biological processes are being implicated in wound repair, tumor invasion and metastasis, and AIDS pathogenesis. We are characterizing the functions of certain key proteins such as PTEN, Slug, and Tat that we hypothesize help regulate cytoskeletal and signaling processes essential for development, malignancy, or AIDS. For example, roles of the tumor suppressor PTEN are being characterized in the regulation of cell interactions, migration, and signal transduction , e.g. in MAP kinase signaling. Roles of HIV Tat in regulating cell adhesion, invasion, and cytokine production are also being defined. We are also collaborating with the Oral and Craniofacial Genome Project to find new relevant genes, and with GTTB, NIDCR to develop an artificial salivary gland. These studies should help to clarify mechanisms of pathogenesis and repair, and identify opportunities for therapeutic intervention in craniofacial congenital defects, cancer, HIV disease, and other disorders.